The purpose of the research program is to study the mechanisms of production of the currently acceptable animals models of chronic bronchitis and emphysema. The method involving the chronic long-term exposure to nitrogen dioxide in concentrations of 2-5, 10-15 and 20-30 ppm with and without dust (fly ash) are studied in hamsters and cats and analyzed by physiologic, pathologic and morphometric methods. Cats are utilized for study of a chronic bronchitis model because of the plentiful distribution of tracheobronchial glands. Papain and elastase models are being studied in specific pathogen free rats to evaluate the role of the circulating leucocyte in the genesis of the emphysema lesion. Methods of decreasing the levels of the serum antiprotease activity are being studied in experimental animals in order to produce an animal model which resembles that of the alpha1-antitrypsin deficiency state with obstructive lung disease in man. These studies will include perturbations of the serum antiprotease activity with and without an induced pulmonary injury. Biochemical studies of lung slices following injuries produced by nitrogen dioxide, high oxygen concentrations and drugs will be performed. The phospholipid and glycoprotein moieties in particular of the lung will be evaluated and correlated with morphometric studies of the Typell cells, laminated inclusions and the bronchial epithelial cells.